Fabio Scarinci

Deep Retinal Capillary Nonperfusion Is Associated With Photoreceptor Disruption in Diabetic Macular Ischemia

PURPOSE To report outer retinal structural changes associated with macular capillary nonperfusion at the level of deep capillary plexus (DCP) in diabetic patients. DESIGN Prospective observational cross-sectional study. METHODS The study included 14 eyes of 10 patients who were diagnosed as having diabetic retinopathy. To study the outer retina and localize areas of capillary nonperfusion at the superficial (SCP) or DCP, we used the spectral-domain optical coherence tomography (SDOCT) device (RTVue-XR Avanti; Optovue Inc, Fremont, California, USA) with split-spectrum amplitude-decorrelation angiography (SSADA) software for optical coherence tomography angiography (OCTA). Two independent masked graders (F.S. and A.A.F.) qualitatively evaluated SDOCT scans as either normal or having outer retina disruption. The angiographic images were examined to define the presence and location of capillary nonperfusion. RESULTS Eight eyes showed outer retinal disruption on SDOCT that co-localized to areas of enlarged foveal avascular zone, areas of no flow between capillaries, and capillary nonperfusion of the DCP. Six eyes without outer retinal changes on SDOCT showed robust perfusion of the DCP. CONCLUSIONS Using OCTA, this study shows that macular photoreceptor disruption on SDOCT in patients with diabetic retinopathy corresponds to areas of capillary nonperfusion at the level of the DCP. This is important in highlighting the contribution of the DCP to the oxygen requirements of the photoreceptors as well as the outer retina in diabetic macular ischemia.

Association of Diabetic Macular Nonperfusion With Outer Retinal Disruption on Optical Coherence Tomography

IMPORTANCE Diabetic macular nonperfusion leads to decreased perifoveal capillary blood flow, which in turn causes chronic ischemia of the retinal tissue. Using point-to-point correlation between spectral-domain optical coherence tomography (SD-OCT) and nonperfusion on fluorescein angiography, we observed that retinal capillary nonperfusion is associated with photoreceptor compromise on OCT. This study highlights a new concept of a possible contribution of the retinal deep capillary plexus to photoreceptor compromise in diabetic retinopathy in the absence of diabetic macular edema. OBJECTIVE To report outer retinal structural changes associated with enlargement of the foveal avascular zone and/or capillary nonperfusion in the macular area of diabetic patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational cross-sectional study in 9 patients who were diagnosed as having diabetic retinopathy without diabetic macular edema and underwent fluorescein angiography and SD-OCT for diabetic retinopathy from July 8, 2014, to December 1, 2014, at a tertiary academic referral center. This analysis was conducted between December 2, 2014, and January 31, 2015. MAIN OUTCOMES AND MEASURES Outer retinal changes on SD-OCT in areas of macular ischemia. RESULTS The study included 13 eyes of 9 diabetic patients (4 men and 5 women aged 34-58 years) with a mean duration of diabetes mellitus of 14.5 years. Nine eyes showed outer retinal disruption revealed by SD-OCT that colocalized to areas of enlargement of the foveal avascular zone and macular capillary nonperfusion. Four fellow eyes with normal foveal avascular zones did not show any retinal changes on SD-OCT. CONCLUSIONS AND RELEVANCE Macular ischemia in diabetic patients can be associated with photoreceptor compromise. The presence of disruption of the photoreceptors on OCT in diabetic patients can be a manifestation of underlying capillary nonperfusion in eyes without diabetic macular edema. Ischemia at the deep capillary plexus may play an important role in these outer retinal changes.

Macular pucker: To peel or not to peel the internal limiting membrane? a microperimetric response

Background: To compare functional and anatomical outcomes after idiopathic macular pucker removal between eyes that underwent internal limiting membrane (ILM) peeling and eyes that did not. Methods: In this multicentric, randomized clinical trial, 60 eyes of 60 patients affected with idiopathic macular pucker were enrolled. Thirty eyes underwent 23-gauge pars plana vitrectomy associated with ILM peeling (“ILM peeling group”), whereas 30 eyes did not undergo ILM peeling (“ILM not peeling group”). Retinal sensitivity, frequency of microscotomas, and all the other microperimetric parameters were tested by MP1 microperimetry. Best-corrected visual acuity was investigated with the Early Treatment Diabetic Retinopathy Study chart. Anatomical outcomes were analyzed with spectral domain optical coherence tomography. Results: After a 12-month follow-up, the mean retinal sensitivity in the 4° central area showed a greater and faster recovery in the ILM not peeling group than in the ILM peeling group (P = 0.041). The number of absolute microscotomas (0 dB) within the 12° central retinal area was significantly higher in the ILM peeling group than in the ILM not peeling group (P = 0.044). Conclusion: The ILM not peeling group seems to show better outcomes than the ILM peeling group as measured by mean retinal sensitivity and number of microscotomas after a 12-month follow-up.

Macular vitreoretinal interface abnormalities in highly myopic eyes with posterior staphyloma: 5-year follow-up.

Purpose: To review prevalence, long-term progression, and prognosis of vitreoretinal interface modifications in pathologic myopia with posterior staphyloma and investigate foveal sensitivity and fixation stability. Methods: Retrospective single-institution series of 214 eyes (116 patients) with pathologic myopia, axial length >30 mm, and posterior staphyloma. Exclusion criteria included follow-up less than five years, incomplete records, and/or less than three optical coherence tomography or microperimetry. Patients were divided into 5 groups according to optical coherence tomography: 1) epiretinal membrane without schisis (ERM); 2) macular retinal schisis (Schisis); 3) partial thickness macular hole (PTMH); 4) full-thickness macular hole (FTMH); and 5) posterior retinal detachment (PRD) with or without macular hole. Disease progression was defined as a visual acuity decrease of two or more lines associated to objective worsening of the optical coherence tomography and/or microperimetry. Results: Vitreoretinal abnormalities at baseline were present in 116 of 204 patients (56.8%) and 214 of 408 eyes (52.4%); 98 of 116 patients (84.4%) showed bilateral involvement. Baseline visual acuity and foveal sensitivity varied significantly with ERM performing better and PRD worse than others; PTMH and FTMH did not differ. During the 66 months of average follow-up, 33 of 214 eyes (15.4%) required surgery and 13 of 33 eyes (39.3%) needed reintervention. Surgery rate significantly differed among groups: 2% for ERM, 20% to 25% for Schisis, PTMH, and FTMH, and up to 50% for PRD. Progression rate of Schisis and FTMH was the same, regardless of symptoms, while macula-off PRD always required surgery. Decrease of fixation stability and foveal sensitivity correlated to need for surgery, while baseline foveal sensitivity and fixation did not. Conclusion: Vitreoretinal interface pathology in pathologic myopia with posterior staphyloma encompasses a spectrum of conditions whose baseline functionality, prognosis, rate, and amount of progression vary significantly. Customized treatment for each different condition should be considered.

Early microvascular retinal changes in optical coherence tomography angiography in patients with type 1 diabetes mellitus

Diabetic retinopathy (DR) can lead to significant vision loss and blindness and has a particularly high prevalence in patients with type 1 diabetes (DM1). In this study, we investigate quantitative differences in optical coherence tomography angiography (OCTA) data between DM1 patients with no or mild signs of retinopathy and non‐diabetic subjects.

Adaptive optics reveals photoreceptor abnormalities in diabetic macular ischemia

Diabetic macular ischemia (DMI) is a phenotype of diabetic retinopathy (DR) associated with chronic hypoxia of retinal tissue. The goal of this prospective observational study was to report evidence of photoreceptor abnormalities using adaptive optics scanning laser ophthalmoscopy (AOSLO) in eyes with DR in the setting of deep capillary plexus (DCP) non-perfusion. Eleven eyes from 11 patients (6 women, age 31–68), diagnosed with DR without macular edema, underwent optical coherence tomography angiography (OCTA) and AOSLO imaging. One patient without OCTA imaging underwent fluorescein angiography to characterize the enlargement of the foveal avascular zone. The parameters studied included photoreceptor heterogeneity packing index (HPi) on AOSLO, as well as DCP non-perfusion and vessel density on OCTA. Using AOSLO, OCTA and spectral domain (SD)-OCT, we observed that photoreceptor abnormalities on AOSLO and SD-OCT were found in eyes with non-perfusion of the DCP on OCTA. All eight eyes with DCP non-flow on OCTA showed photoreceptor abnormalities on AOSLO. Six of the eight eyes also had outer retinal abnormalities on SD-OCT. Three eyes with DR and robust capillary perfusion of the DCP had normal photoreceptors on SD-OCT and AOSLO. Compared to eyes with DR without DCP non-flow, the eight eyes with DCP non-flow had significantly lower HPi (P = 0.013) and parafoveal DCP vessel density (P = 0.016). We found a significant correlation between cone HPi and parafoveal DCP vessel density (r = 0.681, P = 0.030). Using a novel approach with AOSLO and OCTA, this study shows an association between capillary non-perfusion of the DCP and abnormalities in the photoreceptor layer in eyes with DR. This observation is important in confirming the significant contribution of the DCP to oxygen requirements of photoreceptors in DMI, while highlighting the ability of AOSLO to detect subtle photoreceptor changes not always visible on SD-OCT.

Exploring the morphological and functional retinal changes after dexamethasone intravitreal implant (Ozurdex®) in macular edema due to retinal vein occlusion.

Purpose: To explore functional and morphological retinal changes 6 months after dexamethasone intravitreal implant (DEX implant) for the treatment of macular edema due to central or branch retinal vein occlusion (CRVO, BRVO). Procedures: In this prospective interventional case series patients underwent a complete ophthalmological examination at baseline and monthly, including best-corrected visual acuity (BCVA), spectral domain-optical coherence tomography and microperimetry. Fluorescein angiography was performed at baseline and at 4 months. All patients were treated with a DEX implant and retreated according to predefined criteria starting from month 4. Results: Sixteen patients (mean age 66 ± 13 years, 14 CRVO, 2 BRVO) were included. At 6 months mean retinal sensitivity improved from 9.7 ± 4.6 to 13.6 ± 5.4 dB (p < 0.0001) while mean BCVA improved from 52.4 ± 16.2 to 66.1 ± 16.6 (p < 0.0001). Mean central retinal thickness decreased from 708.3 ± 151.01 to 362.7 ± 177.4 μm (p < 0.0001); 56.2% of eyes were retreated at month 4. Conclusions: At 6 months DEX implant led to a significant improvement in retinal sensitivity and visual acuity associated with a reduction of retinal thickness in patients with macular edema due to retinal vein occlusion.

Functional and structural assessment of lamellar macular holes

Aim The purpose of the present work was to evaluate the macular sensitivity of patients with lamellar macular hole (LMH) by means of microperimetry, and to explore the relationships between macular function, LMH anatomical characteristics and vitreous status. Methods A total of 39 eyes from 37 patients with a diagnosis of LMH and 20 age-matched control subjects were enrolled. All patients underwent a complete ophthalmological examination including visual acuity testing (logMAR) and MP1 microperimetry. LMHs were quantitatively and qualitative characterised by spectral domain optical coherence tomography (OCT) in terms of base and apex diameter, depth, central foveal and perifoveal thickness, splitting location and integrity of outer retina layers. B scan ultrasonography was performed in order to characterise the vitreoretinal relationships. Results Mean total (17.2±2.2 vs 19.6±0.5 dB, respectively, p<0.0001) and mean central (16.1±3.2 vs 19.2±0.7 dB, p<0.0001) retinal sensitivity were significantly reduced in LMH eyes in comparison with controls. Best corrected visual acuity (BCVA) (0.15±0.15 vs 0.03±0.06 logMar, p=0.001) and central retinal thickness (329.05±59.3 vs 265±28.5 μm, p<0.0001) were significantly worse in LMH eyes in comparison with controls. In our population, mean total and central retinal sensitivity showed a moderately significant relationship with LMH depth (R2 0.18, p=0.006, R2 0.14, p=0.02, respectively). In all, 38% of LMH eyes (15/39) showed focal interruptions of the inner–outer segment junction with lower values of BCVA and macular sensitivity. An incomplete posterior vitreous detachment with vitreopapillary adhesion was found in 48.7% (19/39) of patients with LMH. Conclusions Eyes with LMH show an impaired macular function, which is partially related to LMH depth and is more pronounced in eyes with outer retinal layers abnormalities.

Single retinal layer evaluation in patients with type 1 diabetes with no or early signs of diabetic retinopathy: The first hint of neurovascular crosstalk damage between neurons and capillaries?

Purpose: To analyze the retinal-choroidal changes in type 1 diabetes mellitus (DM1) patients with no or early signs of diabetic retinopathy (DR). Methods: Seventy-six eyes of 38 DM1 patients and 26 control eyes were included. Nine individual retinal layer thickness measurements were obtained using the spectral domain-optical coherence tomography automated segmentation algorithm. Results: The retinal nerve fiber layer was slightly thinner in all explored quadrants, even if the reduction was not significant in DM1 eyes versus control eyes. The inner nuclear layer (INL) thickness was thicker in all DM1 eyes versus control eyes in all quadrants (p < 0.050). Analyses adjusting for inner retinal thickness in all sectors confirmed INL thickening by about 4%, and also found a significant thinning of the ganglion cell layer (GCL) by about 3.5% in all DM1 subjects versus controls (p < 0.050). Conclusion: DM1 patients with no or early signs of DR present retinal changes particularly at the INL and GCL that might be correlated to initial findings of neurodegeneration.

Analysis of Functional Dissociations between Best Corrected Visual Acuity and Microperimetric Parameters in Neovascular Age-Related Macular Degeneration Patients Underwent to Three Monthly Ranibizumab Injections

Background: To analyze the sensitivity of best corrected visual acuity and microperimetry to detect significant visual changes after 3 intravitreal ranibizumab in exudative age-related macular degeneration. Design: Prospective, open-label study. Participants: 50 eyes of 50 naive patients affected by neovascular age-related macular degeneration were enrolled. Methods: Enrolled patients underwent to a loading phase of 3 monthly intravitreal injections of ranibizumab. Best-corrected visual acuity was investigated with the ETDRS chart at 4 m. Central retinal sensitivity was tested with microperimetry using a Goldmann III stimulus to 33 points over the 12° central of the macula with a 4-2 double staircase strategy. Main outcome measures: Comparison of changes in mean 4° central retinal sensitivity and best-corrected visual acuity in “BCVA relatively stable patients” (defined as change ≤ ± 4 ETDRS letters after treatment). Analysis of a possible relationship between changes in best-corrected visual acuity and 4° central retinal sensitivity in “mean 4° central retinal sensitivity relatively stable patients” (defined as change in mean retinal sensitivity ≤ ± 2dB) Results: Mean best-corrected visual acuity improved of 5.90 ± 11.29 ETDRS letters (P=0.0006). Total mean retinal sensitivity improved +1.59 ± 2.12 dB (P<0.0001), while in the 4° central retinal area the increase was +1.36 ± 3.45 dB (P=0.0078). 38% of patients (19 eyes) were considered as “BCVA relatively stable patients”. In this subgroup, Pearson’s correlation analysis showed a direct correlation between changes observed with both methods (r = 0.71; P = 0.002). 48% of patients (24 eyes) were considered as “Mean 4° central retinal sensitivity relatively stable patients”. In this subgroup, Pearson’s correlation analysis didn’t show a relationship between changes observed with both methods (r = 0.11; P = 0.56). Conclusions: Microperimetry central retinal sensitivity seems to be an important to complete the functional evaluation in patients with wet age-related macular degeneration after 3 intravitreal ranibizumab.